Help Privacy Policy Disclaimer
  Advanced SearchBrowse




Journal Article

Body temperature variation controls pre-mRNA processing and transcription of antiviral genes and SARS-CoV-2 replication


Los,  Bruna       
IMPRS for Biology and Computation (Anne-Dominique Gindrat), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)

NucleicAcidsRes_Los et al_2022.pdf
(Publisher version), 5MB

Supplementary Material (public)
There is no public supplementary material available

Los, B., Preußner, M., Eschke, K., Vidal, R. M., Abdelgawad, A., Olofsson, D., et al. (2022). Body temperature variation controls pre-mRNA processing and transcription of antiviral genes and SARS-CoV-2 replication. Nucleic Acids Research, 50(12), 6769-6785. doi:10.1093/nar/gkac513.

Cite as: https://hdl.handle.net/21.11116/0000-000E-568A-6
Antiviral innate immunity represents the first defense against invading viruses and is key to control viral infections, including SARS-CoV-2. Body temperature is an omnipresent variable but was neglected when addressing host defense mechanisms and susceptibility to SARS-CoV-2 infection. Here, we show that increasing temperature in a 1.5°C window, between 36.5 and 38°C, strongly increases the expression of genes in two branches of antiviral immunity, nitric oxide production and type I interferon response. We show that alternative splicing coupled to nonsense-mediated decay decreases STAT2 expression in colder conditions and suggest that increased STAT2 expression at elevated temperature induces the expression of diverse antiviral genes and SARS-CoV-2 restriction factors. This cascade is activated in a remarkably narrow temperature range below febrile temperature, which reflects individual, circadian and age-dependent variation. We suggest that decreased body temperature with aging contributes to reduced expression of antiviral genes in older individuals. Using cell culture and in vivo models, we show that higher body temperature correlates with reduced SARS-CoV-2 replication, which may affect the different vulnerability of children versus seniors toward severe SARS-CoV-2 infection. Altogether, our data connect body temperature and pre-mRNA processing to provide new mechanistic insight into the regulation of antiviral innate immunity.